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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition

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Author(s):
Coronado, Monika Aparecida [1] ; Eberle, Raphael Josef [1] ; Bleffert, Nicole [2, 3] ; Feuerstein, Sophie [2, 3] ; Olivier, Danilo Silva [1] ; de Moraes, Fabio Rogerio [1] ; Willbold, Dieter [2, 3] ; Arni, Raghuvir Krishnaswamy [1]
Total Authors: 8
Affiliation:
[1] Univ Estadual Paulista, UNESP, Dept Phys, Multiuser Ctr Biomol Innovat, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Forschungszentrum Julich, Inst Complex Syst Struct Biochem ICS 6, Julich - Germany
[3] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, Univ Str, Dusseldorf - Germany
Total Affiliations: 3
Document type: Journal article
Source: Antiviral Research; v. 160, p. 118-125, DEC 2018.
Web of Science Citations: 6
Abstract

Zika virus infection is the focus of much research due to the medical and social repercussions. Due the role of the viral NS2B/NS3 proteinase in maturation of the viral proteins, it had become an attractive antiviral target. Numerous investigations on viral epidemiology, structure and function analysis, vaccines, and therapeutic drugs have been conducted around the world. At present, no approved vaccine or even drugs have been reported. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified the polyanion suramin, an approved antiparasitic drug with antiviral properties, as a potential inhibitor of Zika virus complex NS2B/NS3 proteinase with IC50 of 47 mu M. Using fluorescence spectroscopy results we could determine a k(d) value of 28 mu M and had shown that the ligand does not affect the thermal stability of the protein. STD NMR spectroscopy experiments and molecular docking followed by molecular dynamics simulation identified the binding epitopes of the molecule and shows the mode of interaction, respectively. The computational analysis showed that suramin block the Ser135 residue and interact with the catalytically histidine residue. (AU)

FAPESP's process: 16/08104-8 - Structural and functional aspects of two DNA binding proteins encoded by Corynebacterium pseudotuberculosis
Grantee:Raphael Josef Eberle
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/13765-0 - Structural Studies and Characterization of Proteins by X-ray Crystallography and Nuclear Magnetic Resonance. Structural investigations and biophysics of molecular mechanisms of functional proteins.
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Regular Research Grants
FAPESP's process: 15/18868-2 - Multi-user equipment acquisition for molecular and structural biology
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
Grantee:Raghuvir Krishnaswamy Arni
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 16/12904-0 - Mechanism and Molecular Interactions of Bioactive molecules with NS3 protease from Zika virus.
Grantee:Monika Aparecida Coronado
Support Opportunities: Scholarships in Brazil - Post-Doctoral